Modeling Kinase Inhibition Using Highly Confident Data Sets

Protein kinases form a consistent class of promising drug targets, and several efforts have been made to predict the activities of small molecules against a representative part of the kinome. This study continues our previous work (Bora, A.; Avram, S.; Ciucanu, I.; Raica, M.; Avram, S. Predictive Models for Fast and Effective Profiling of Kinase Inhibitors. J. Chem. Inf. Model. 2016, 56, 895−905; www.chembioinf.ro) aiming to build and measure the performance of ligand-based kinase inhibitor prediction models. Here we analyzed kinase–inhibitor pairs with multiple activity points extracted from the ChEMBL database and identified the main sources of inconsistency. Our results indicate that lower IC50 values are usually less affected by errors and reflect more accurately the structure–activity relationship of the molecules against the target, ideally for quantitative structure–activity relationship studies. Further, we modeled the activities of 104 kinases using unbiased target-specific activity points. The p...